Background: The catechol-O-methyl-transferase (COMT) inhibitor nitecapone, which prevents mucosal degradation of dopamine, and some dopamine receptor agonists ameliorate gastroduodenal mucosal damage. Therefore, their effects on mucosal bicarbonate secretion were studied. Methods: Duodenum just distal to the Brunner's glands area was cannulated in situ in anesthetized rats. Bicarbonate secretion into the luminal perfusate and transmucosal electrical potential difference (PD) were recorded. Results: Intravenous dopamine (50 μg · kg⁻¹ · h⁻¹) increased bicarbonate secretion twofold, and a higher rate of infusion (250 μg · kg⁻¹ · h⁻¹) resulted in a further increase. Neither dose affected the PD. The dopamine D1 agonist SKF-38393 (10–50 μg/kg) and the COMT inhibitor nitecapone (50–500 μg/kg) caused dose-dependent increases in secretion, similar to that observed with dopamine. Domperidone, a peripherally acting dopamine antagonist, inhibited the stimulatory effects of SKF-38393 and nitecapone. Hexamethonium or the α-adrenoceptor antagonist phentolamine, in contrast, did not affect the response to nitecapone. Intracerebroventricular administration of nitecapone was without effect. Conclusions: A probable electroneutral component of duodenal mucosal bicarbonate secretion is stimulated via peripheral dopamine D1 receptors. This may contribute to the previously observed ulceroprotective actions of dopaminergic compounds.